This proposal is in response to RFA-DA-10-016(R01) Medications Development for Cannabis-Related Disorders. Consistent with the goals of this RFA, the overall goal of the proposed project is to assess the impact of transdermal nicotine patch (TNP) treatment on marijuana (MJ) withdrawal (negative affect and craving motivated by negative affect) symptoms in MJ-dependent individuals. The aim of this proposal is to accurately assess the effects of TNP on MJ withdrawal symptoms across 15 days of biochemically confirmed MJ abstinence using a placebo-controlled, double-blind, randomly assigned treatment design. To achieve these goals, 116 carefully screened cannabis-dependent individuals (58 female) will be randomly assigned to one of two doses (0 mg or 7mg nicotine) of TNP while they abstain from MJ for 15 days. Large financial contingencies will be used to provide a high degree of abstinence and study completion. This will be the first adequately powered study to assess the effects of TNP on MJ negative affect-related withdrawal symptoms and urges to use MJ. Withdrawal patterns and abstinence will be assessed in two groups of MJ-dependent individuals: 1) those who rarely or never smoke tobacco, and 2) those who smoke four or fewer tobacco cigarettes per day (very light tobacco smokers). A stratified randomization method will be used to control for gender and tobacco-smoker status. It is hypothesized that MJ withdrawal symptoms will be less severe in the group assigned to the 7 mg patch than in the group assigned to the placebo. It is also hypothesized that individuals high in anxiety/neuroticism and those high in aggression/hostility will exhibit greater benefits from TNP than those low in these traits. Given that no gender differences were observed in our preliminary study, gender differences are not predicted. The over-the-counter availability, minimal abuse risks, and minimal adverse side-effects associated with TNP would make it an ideal and highly implementable treatment for MJ dependence if it can be demonstrated to be efficacious in reducing MJ withdrawal symptoms. Sometimes simple solutions are the best. PUBLIC HEALTH RELEVANCE: Marijuana dependence increases risks for a variety of psychosocial and medical problems and withdrawal symptoms associated with attempts to quit using marijuana appear to be an important obstacle to quitting for many of the increasing number of marijuana dependent individuals in the United States. Our study would test the important possibility that a pharmacotherapy with a very low abuse potential, transdermal nicotine patch (TNP), is efficacious in reducing marijuana withdrawal symptoms across a 15-day period of abstinence in marijuana-dependent individuals. The rationale for testing the efficacy of TNP in reducing marijuana withdrawal symptoms is based on preliminary evidence from our laboratory suggesting that TNP may be able to reduce these symptoms, as well as evidence from a number of laboratories indicating that marijuana withdrawal symptoms largely parallel those of tobacco withdrawal symptoms both in terms of nature and severity. Our preliminary findings suggest that TNP reduces negative affect and negative affect-motivated urge to use marijuana during abstinence from marijuana in MJ-dependent-users (including those who do not use tobacco). Thus, there is reason to believe that TNP could also assist treatment-seeking marijuana dependent individuals in maintaining marijuana abstinence, whether or not they are tobacco smokers. Sometimes the simplest solutions are the best.